MOLECULAR GENETIC ANALYSIS OF ALCOHOL RESPONSE

  • Crabbe, John Jr (PI)

Project: Research project

Project Details

Description

Peripherally administered arginine vasopressin (AVP) affects tolerance to
EtOH hypothermia in mice chronically administered EtOH. Such effects of
AVP are mediated by the central nervous system and are not due to changes
in EtOH metabolism. These effects of AVP may depend upon intact
serotonergic projections from the median raphe nucleus to the hippocampus
and may be mediated through VI receptors. Sensitivity and tolerance to
the hypothermic effect of EtOH are known to be influenced markedly by
genotype. In a panel of 20 inbred strains of mice, both qualitative and
quantitative differences were seen, for some strains developed no
tolerance over the 8 day treatment period. An AVP analog without
peripheral hormonal effects influenced the pattern of genetic control
over hypothermic sensitivity and tolerance in a panel of recombinant
inbred (RI) mice. The proposed research will attempt to link these two
areas of research which have been independently investigated. It is
hypothesized that the genetic differences in EtOH sensitivity and
tolerance development may be in part due to differences in AVP systems.
The proposed research will attempt to test this hypothesis employing
molecular genetic tools for studying AVP gene expression in the same
panel of inbred strains of mice. Dr. Crabbe, the Visiting Researcher,
will learn to employ the techniques of RNA extraction, Northern blotting,
cDNA library development, cDNA clone development and characterization,
solution hybridization, and RFLP development and analysis with Southern
blotting during a 6 month stay in the laboratory of Dr. Milner, the Host.
These techniques will be used to characterize brain AVP gene activity in
the panel of 20 inbred strains of mice which Dr. Crabbe has previously
characterized for sensitivity and tolerance development to EtOH-induced
hypothermia. The potential relationship between AVP gene activity and
EtOH hypothermia will be assessed by genetic correlational analysis. cDNA
clones for the gene in mice will be developed, and an attempt will be
made to map the gene in mice.
StatusFinished
Effective start/end date9/29/899/28/90

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)

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